Substance use disorders in adults commonly have their onset in adolescence, with earlier onset predicting subsequent development of dependency and abuse. Our long-term objectives here are reduction of substance use disorders through an improved understanding of the precursors of early initiation of substance use by adolescents. We propose exploration of the neurocognitive precursors of early substance use, hypothesizing that particular neurocognitive characteristics will predict adolescent drug-use trajectories. We target exploration of prefrontal cortex (PFC) function, as the PFC is notable for its prolonged period of postnatal maturation and for its involvement in decision-making, self-regulation, and impulsivity -- traits common to adolescents and to substance users. This 5-year investigation, designed as a multicohort observational longitudinal project, proposes the following specific aims: 1) to map the developmental trajectory of prefrontally-mediated cognitive functions; 2) to examine the relation between laboratory measures of prefrontal cognitive functions and measures of impulsivity, and to map the developmental trajectory of impulsivity; and 3) to investigate the role of prefrontal cortex function and impulsivity in early drug use and in various adolescent drug-use trajectories. In an urban, mixed socioeconomic status sample, three groups of 175 subjects will be enrolled at the following ages 10, 11, and 12 years, for a total of 525 subjects. Each group will be followed for 5 years. On four occasions subjects will be administered a battery of neuro-cognitive tasks and measures of impulsivity, will complete an assessment of risk behaviors, a self-assessment for pubertal stage, and provide a urine sample for drug screening. The major data analysis strategy will use mixture models to calculate differential trajectories of development of the prefrontal cortex and impulsivity as well as drug use initiation. At project end we anticipate improved understanding of the neurocognitive precursors of adolescent drug use. This, in turn, will provide an infrastructure for developing prevention strategies.